Multiple acquisitions of CTX-M plasmids in the rare D2 genotype of Escherichia coli provide evidence for convergent evolution

Microbiology (Reading). 2009 May;155(Pt 5):1656-1668. doi: 10.1099/mic.0.023234-0. Epub 2009 Apr 9.


Over the last decade, CTX-M enzymes have become the most prevalent extended-spectrum beta-lactamases (ESBLs) worldwide, mostly in Escherichia coli, causing a major health problem. An epidemiological relationship has been established between a rare genotype of E. coli, the D(2) genotype, and the presence of CTX-M genes. We investigated this striking association by exploring the genetic backgrounds of 18 D(2) genotype CTX-M-producing strains and of the plasmids encoding CTX-M enzymes. The 18 strains had different genetic backgrounds, as assessed by multilocus sequence and O typing, and were associated with various plasmids bearing diverse CTX-M genes. The region encompassing the genetic marker of the D(2) genotype (TSPE4.C2) was not correlated with the presence of CTX-M genes. CTX-M-producing D(2) strains had far fewer virulence factors than a control group of 8 non-ESBL-producing D(2) strains, and an inverse relationship was found between the number of co-resistances associated with the CTX-M gene and the number of virulence factors found in the strain. These findings provide evidence for multiple acquisitions of plasmids carrying CTX-M genes in different D(2) genotype strains. They strongly suggest that convergent evolution has occurred, and indicate that there has been selection for the association of a specific genetic background of the strain and the CTX-M gene. This fine-tuning of the relationship between the D(2) genotype and CTX-M genes presumably increases the fitness of the strain, indicating a role for the host cell in the acquisition and dissemination of CTX-M genes.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Drug Resistance, Bacterial
  • Escherichia coli / classification
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Evolution, Molecular*
  • Genotype
  • Microbial Sensitivity Tests
  • Phylogeny
  • Plasmids / genetics*
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism


  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • beta-Lactamases